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1.
Cell Tissue Res ; 367(2): 257-267, 2017 02.
Artigo em Inglês | MEDLINE | ID: mdl-27844205

RESUMO

Osteoporosis, which is a systemic skeletal disease characterized by low bone mineral density and microarchitectural deterioration of bone quality, is a global and increasing public health problem. Recent studies have suggested that Tenuigenin (TEN), a class of native compounds with numerous biological activities such as anti-resorptive properties, exerts protective effects against postmenopausal bone loss. The present study aims to investigate the osteogenic effects of TEN on bone mesenchymal stem cells (BMSCs) in vitro and in vivo. Alkaline phosphatase (ALP) activity/staining, Alizarin red staining and the expression of osteogenic markers, including runt-related transcription factor 2, osterix, osteocalcin, collagen Iα1, ß-catenin and glycogen synthase kinase-3ß were investigated in primary femoral BMSCs from C57/BL6 mice cultured under osteogenic conditions for 2 weeks to examine the effects of TEN. An ovariectomized (OVX) mouse model was used to investigate the effect of TEN treatment for 3 months in vivo. We found that ALP activity, mineralized nodules and the expression of osteogenic markers were increased and WNT/ß-catenin signaling was enhanced in vitro and in vivo. Bone parameters, including trabecular thickness, trabecular number and bone mineral density were higher in the OVX+TEN group than in control OVX mice. Our results suggest the therapeutic potential of TEN for the treatment of patients with postmenopausal osteoporosis.


Assuntos
Osso e Ossos/citologia , Diferenciação Celular/efeitos dos fármacos , Medicamentos de Ervas Chinesas/farmacologia , Células-Tronco Mesenquimais/citologia , Osteogênese/efeitos dos fármacos , Animais , Biomarcadores/metabolismo , Reabsorção Óssea/patologia , Subunidade alfa 1 de Fator de Ligação ao Core/genética , Subunidade alfa 1 de Fator de Ligação ao Core/metabolismo , Medicamentos de Ervas Chinesas/química , Feminino , Fêmur/citologia , Células-Tronco Mesenquimais/efeitos dos fármacos , Células-Tronco Mesenquimais/metabolismo , Camundongos Endogâmicos C57BL , Modelos Biológicos , Osteocalcina/genética , Osteocalcina/metabolismo , Ovariectomia , Fator de Transcrição Sp7 , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Via de Sinalização Wnt/efeitos dos fármacos
2.
Huan Jing Ke Xue ; 37(6): 2131-2140, 2016 Jun 08.
Artigo em Chinês | MEDLINE | ID: mdl-29964878

RESUMO

The concentrations of 16 organochlorine pesticides (OCPs) in 7 water samples collected from different sites of water source areas of Guangdong and Guangxi were detected by SPE-GC-MS, and then the pollution characteristics were analyzed. This study established species sensitivity distribution(SSD) curves with BurrⅢ distribution model. In the meantime, HC5 values were calculated by BurrliOZ software, which were used to evaluate the toxicity effects of OCPs towards aquatic organisms. Finally, margin of safety concentration values were calculated to assess the ecological risk. The results showed that the concentration of OCPs varied from 6.64 to 34.19 ng·L-1, with a mean value of 16.76 ng·L-1, while HCHs and DDTs contributed a lot. HCHs were predominately originated from lindane, which is a component in household insecticide, while DDTs were from dicofol contamination or historical residues. Vertebrates could stand severer toxicity in comparison with invertebrates. α-endosulfan showed a greater toxicity towards aquatic plants and microorganisms than others, while p, p'-DDT turned out to be the most hazardous pollutant to vertebrates and invertebrates among the 16 OCPs studied. Generally speaking, OCPs in study areas didn't show conspicuous ecological risks towards aquatic organisms, DDTs and α-endosulfan, however, are still worth paying close attention due to their high potential risks.


Assuntos
Monitoramento Ambiental , Hidrocarbonetos Clorados/toxicidade , Praguicidas/toxicidade , Poluentes Químicos da Água/toxicidade , Animais , China , DDT , Ecotoxicologia , Hexaclorocicloexano , Medição de Risco , Testes de Toxicidade , Água
3.
Drug Des Devel Ther ; 9: 5169-83, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26392752

RESUMO

Osteoporosis is a systemic skeletal disease that is characterized by low bone density and microarchitectural deterioration of bone tissue. The increasing prevalence of osteoporosis has attracted much attention. In this study, MC3T3-E1 pre-osteoblasts were treated with the natural compound, baicalein (0.1 µmol/L, 1 µmol/L, 10 µmol/L), to stimulate differentiation over a 14-day period. In addition, a canonical ovariectomized (OVX) mouse model was used to investigate the effect of 3-month baicalein treatment (10 mg/kg per day) in preventing postmenopausal osteoporosis. In vitro, we found that baicalein induced activation of alkaline phosphatase, stimulated the mammalian target of rapamycin complex 1 (mTORC1) signaling pathway, and induced expression of osteoblast differentiation markers, ie, osteocalcin, osterix, collagen Iα1, and runt-related transcription factor 2 (RUNX2), in osteoblasts. In vivo, several bone parameters, including trabecular thickness, trabecular bone mineral density, and trabecular number, in the distal femoral metaphysis were significantly increased in OVX mice treated intragastrically with baicalein for 3 months compared with OVX mice that were not treated with baicalein. We also found that expression of osteocalcin and RUNX2 was decreased in primary ossified tissue from the OVX group, and baicalein increased the levels of osteocalcin and RUNX2 in OVX mice. These data suggest that baicalein can stimulate MC3T3-E1 cells to differentiate into osteoblasts via activation of the mTORC1 signaling pathway, which includes protein kinases and transcription factors such as P-4E/BP1 and P-S6K1.


Assuntos
Flavanonas/farmacologia , Complexos Multiproteicos/metabolismo , Osteoblastos/efeitos dos fármacos , Osteogênese/efeitos dos fármacos , Serina-Treonina Quinases TOR/metabolismo , Animais , Linhagem Celular , Subunidade alfa 1 de Fator de Ligação ao Core/metabolismo , Relação Dose-Resposta a Droga , Feminino , Flavanonas/administração & dosagem , Humanos , Alvo Mecanístico do Complexo 1 de Rapamicina , Camundongos , Camundongos Endogâmicos C57BL , Osteoblastos/metabolismo , Osteocalcina/metabolismo , Osteoporose Pós-Menopausa/prevenção & controle , Ovariectomia
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